During narcotic blockade with oral naltrexone in postaddicts, some patients may at times resort to the use of non-narcotic abuse drugs, such as cocaine, amphetamine, and diazepam, as well as alcohol. Although it is possible that interactions between naltrexone and the other drugs might qualitatively or quantitatively interfere with the narcotic blockading action of naltrexone, it is difficult to investigate these possible drug reactions in man. Consequently, a program of studies on this problem has been undertaken in animals and is now in progress. One of the findings thus far is that although neither cocaine nor amphetamine prevents the oral naltrexone blockade of morphine on the mouse Straub tail test, the amount of naltrexone required is increased threefold or more. This increase is apparently due in large part to the potentiation of the morphine Straub tail production by cocaine or amphetamine. In as much as there may be some correlation between the Straub tail effect and the initial narcotic "rush" in man, the proposed research objectives are: (1) to determine the effect of the other currently used stimulant drugs, such as methamphetamine, methylphenidate (Ritalin), and anorexigenics like phenmetrazine (Preludin), upon the narcotic blockading efficacy of oral naltrexone on the morphine Straub tail in mice; (2) to compare these results with the narcotic blockading efficacy of naltrexone as tested by prevention of morphine narcosis in rats; and (3) to examine the hypothesis that the mouse Straub tail test might correlate with the initial narcotic "rush" in man, whereas the rat narcosis test might be analogous to the subsequent "on the nod" depressant phase. A fourth objective is to continue work on the use of diazepam (Valium) and other drugs as antidotes for possible naltrexone acute toxicity and to extend the present encouraging mouse work to other species.